The serum oestradiol/progesterone ratio on the day of OPU + 7, but not the day of OPU + 5, affects the rates of live birth in fresh blastocyst embryo transfer cycles

Abstract

Background: In an in vitro fertilization (IVF) cycle, the embryo ends its wandering time and begins the process of implantation into the uterine cavity on the seventh day after oocyte pick-up (OPU + 7), which is closer than OPU + 5 to the time of nidation. Therefore, measuring the oestradiol (E2)/progesterone (P) ratio on OPU + 7 may be helpful for predicting pregnancy outcomes.

Methods: This is a retrospective cohort study of 2,257 women undergoing a follicular-phase depot gonadotropin-releasing hormone agonist (GnRH-a) protocol for in vitro fertilization /intracytoplasmic sperm injection (IVF/ICSI) treatment and fresh blastocyst embryo transfer cycles at a university-affiliated fertility center between January 2016 and April 2021. First, 2,257 women were split into two groups based on clinical pregnancy for analyzing the levels of E₂ and P and the E₂/P ratio on the day of OPU + 2, OPU + 5 and OPU + 7. And then 2,257 cycles were stratified into three groups based on E₂/P ratio tertiles on OPU + 7: the low group (1.3-15.7 pg/ng), middle group (15.7-28.8 pg/ng), and high group (28.8-487.2 pg/ng). The threshold effect of the E₂/P ratio on OPU + 7 on live birth was investigated using a two-piecewise linear regression model and a smoothing function curve.

Results: The level of P in the clinical pregnancy group were lower than that in the nonclinical pregnancy group on both OPU + 2 and OPU + 7 (201.9 ± 71.6 ng/ml vs 213.1 ± 77.6 ng/ml, 89.5 ± 88.5 ng/ml vs 99.5 ± 94.9 ng/ml, P < 0.05). The E₂/P ratio in the clinical pregnancy group were higher than that in the nonclinical pregnancy group on both OPU + 2 and OPU + 7 (8.4 ± 6.5 pg/ng vs 8.0 ± 6.8 pg/ng, 32.3 ± 38.5 pg/ng vs 25.2 ± 31.0 pg/ng, P < 0.01). The E₂/P ratio on OPU + 7 was positively associated with positive hCG (adjusted OR = 1.01; 95% CI, 1.01-1.02; P < 0.0001), clinical pregnancy (adjusted OR = 1.01; 95% CI, 1.00-1.01; P = 0.0067) and live birth (adjusted OR = 1.01; 95% CI, 1.00-1.01; P < 0.001), and a nonlinear correlation was observed between the E₂/P ratio and LBR on OPU + 7.

Conclusions: A higher E₂/P ratio is associated with a higher LBR, but the E₂/P ratio should be maintained within a suitable range.

Keywords: Estradiol; Hormones; In vitro fertilization; Luteal phase; Progesterone.